The broad, long-term objective of this project is to enhance markedly the understanding of the biological and clinical implications of chromosome alterations in human non-small cell lung cancer (NSCLC) and mesothelioma, two neoplasms for which the current cytogenetic data base is relatively sparse. Karyologic investigations will be performed on a series of tumors from patients with NSCLC or mesothelioma, with emphasis on analyses of untreated primary tumors. This project proposes to identify recurrent chromosome abnormalities in these tumors and correlate the genetic alterations with important clinicopathologic features such as tumor cell phenotype, disease stage, subsequent metastatic behavior, and survival. Long-term tumor cultures and cell lines will be established, and the possibility that specific chromosome alterations correlate with various biological parameters such as spontaneous metastatic ability and in vitro invasiveness in these cell lines will be explored. An inherent component of the overall goal of this project is the evaluation of newer tumor cell culture methods, growth of tumor cell xenografts in athymic mice, and "interphase cytogenetics" techniques (using fluorescence in situ hybridization) to enhance karyologic investigations in these tumors. The molecular and functional characterization of several recurrent sites of chromosome loss previously identified cytogenetically in NSCLC and mesothelioma is also proposed. The frequency of loss of heterozygosity at specific chromosomal sites that have been implicated as "hot spots" for apparently unbalanced structural rearrangements in NSCLC will be determined. Furthermore, the incidence and minimal region of overlap of allelic loss on chromosome regions 1p, 3p, and 22q in mesothelioma will also be investigated. Results of karyotypic analysis of these same tumors will be used to assist in the interpretation of the loss of heterozygosity data. Finally, this project proposes to examine whether tumorigenicity of mesothelioma cell lines exhibiting loss of lp, 3p, or 22q can be suppressed or modulated by microcell-mediated transfer of one or more normal homologs of these chromosomes.